N-乙酰-L-半胱氨酸对小鼠急性酒精性脂肪肝的保护作用

Objective: To investigate the roles of N-acetyl-L-cysteine (NAC) against binge drinking-induced fatty liver in mice. Methods: SPF male C57BL/6 mice were randomly divided into 3 groups, i.e. control group, model group, and NAC/ethanol group (n=10). Mice in model and NAC/ethanol groups were exposed to 3 doses of ethanol (6 g/kg bw) to induced fatty liver, while mice in control group received equal volume and equal energy of maltodextrin solution. NAC was administered to mice at 1 h before ethanol exposure (100 mg/kg bw, i.p.). The mice were sacrificed at 6 h after the last ethanol exposure. The liver and epididymal adipose tissues were collected. Histopathological examination and biochemical assay kit were used to evaluate the fat accumulation, while Western-blot was performed to detect the protein levels of some key factors involved in fat metabolism in liver and adipose tissues. Results: Compored with control group mice, the liver index and liver weight were significantly increased compared with model group, the liver index and TG level in NAC/ethanol group mice were all significantly decreased (P<0.05). Histological examination showed NAC effectively suppressed binge drinking-induced fat accumulation in mice liver. In addition, NAC had no significant effects on the protein levels of peroxisome proliferator-activated receptor-α (PPAR-α), Acy-CoA oxidase (ACOX), sterol regulatory element binding protein 1 c (SREBP-1c) and fatty acid synthase (FAS). Furthermore, the protein levels of hormone sensitive lipase (HSL) did not significantly differ among 3 groups, whereas NAC prevented binge drinking-induced increase of HSL phosphorylation at ser563 and ser660. Conclusion: NAC could effectively attenuate binge drinking-induced fatty liver, which might be associated with the inhibition of lipid mobilization by suppressing the phosphorylation of HSL.目的： 研究抗氧化剂N-乙酰-L-半胱氨酸（N-acetyl-L-cysteine，NAC）对小鼠酒精性脂肪肝（alcoholic fatty liver，AFL）的保护作用。 方法： SPF级雄性C57BL/6小鼠随机分为对照组、模型组及NAC干预组，每组10只。模型组及NAC干预组小鼠连续灌胃给予3次6 g/kg乙醇口服诱导急性AFL，对照组小鼠给予等体积等能量的麦芽糖糊精溶液。NAC在每次乙醇染毒前1 h腹腔注射给予100 mg/kg。末次乙醇染毒后6 h，处死小鼠取肝脏和附睾脂肪组织；病理学检查肝脏脂肪蓄积情况，生化试剂盒测定肝脏甘油三酯（triglyceride，TG）含量；Western-blot测定相关蛋白的表达。 结果： 与对照组小鼠比较，模型组小鼠肝脏明显增大，肝重及肝脏系数明显增加，差异有统计学意义（P<0.05）。与模型组比较，NAC干预组小鼠肝脏系数和肝组织TG含量明显降低，差异有统计学意义（P<0.05）。病理学检查结果显示，模型组小鼠肝脏切片中有大量橙红色的脂滴，而NAC干预组小鼠肝脏切片中脂肪滴明显减少。与模型组比较，NAC干预组小鼠肝脏中过氧化物酶体增殖物活化受体α（PPAR-α）、乙酰辅酶A氧化酶（ACOX）略有减少，固醇调节元件结合蛋白-1c（SREBP-1c）、脂肪酸合成酶（FAS）的蛋白含量无明显改变。附睾脂肪中激素敏感性脂肪酶（HSL）总蛋白在3组小鼠之间未见明显差异。NAC干预组小鼠脂肪组织中p-HSL(ser563)和p-HSL(ser660)的蛋白含量较模型组小鼠明显降低，差异有统计学意义（P<0.05）。 结论： 预先给予NAC可以明显减轻急性乙醇染毒导致的小鼠肝脏中TG的蓄积，其作用可能与抑制外周脂肪动员有关。.